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Cardiovascular toxicities associated with vascular endothelial growth factor receptor tyrosine kinase inhibitors: a pharmacovigilance study based on FDA adverse event reporting system

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Abstract

Background

Vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKIs) are widely used in the treatment of various cancers. However, post-marketing evidence regarding their cardiovascular toxicities remains limited.

Aim

This pharmacovigilance study aimed to comprehensively evaluate the association between VEGFR-TKIs and cardiovascular toxicities in cancer patients.

Method

We retrieved and analyzed cardiovascular toxicity reports related to VEGFR-TKIs from the FDA Adverse Event Reporting System (FAERS). Disproportionality analyses were performed using the proportional reporting ratio (PRR), reporting odds ratio (ROR), information component (IC), and empirical Bayes geometric mean (EBGM) to detect safety signals of cardiovascular toxicities associated with VEGFR-TKIs.

Results

A total of 12,726 cancer patients experienced cardiovascular toxicities associated with VEGFR-TKI treatment. All eleven VEGFR-TKIs were associated with cardiovascular toxicities, with hypertension being the most consistently reported event across all agents. Among them, cabozantinib was associated with the highest number of cardiovascular events, whereas lenvatinib exhibited the strongest signal. Notably, lenvatinib was associated with cardiac failure (ROR = 2.521, PRR = 2.479, IC = 1.308, EBGM = 2.476) and cardiomyopathy (ROR = 2.801, PRR = 2.788, IC = 1.476, EBGM = 2.782); sunitinib with cardiac failure (ROR = 2.745, PRR = 2.693, IC = 1.426, EBGM = 2.687) and cardiomyopathy (ROR = 3.020, PRR = 3.004, IC = 1.584, EBGM = 2.997); ponatinib with cardiomyopathy (ROR = 3.393, PRR = 3.372, IC = 1.752, EBGM = 3.368); and vandetanib with Torsade de pointes/QT prolongation (ROR = 27.930, PRR = 26.101, IC = 4.703, EBGM = 26.051).

Conclusion

VEGFR-TKIs were associated with cardiovascular toxicities, particularly hypertension. Notably, lenvatinib and sunitinib were associated with cardiac failure and cardiomyopathy, ponatinib with cardiomyopathy, and vandetanib with Torsade de pointes and QT prolongation. Future prospective studies are warranted to further clarify the causal relationships between these agents and cardiovascular toxicities.

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Acknowledgements

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Funding

This work was supported by Natural Science Foundation of Gansu Province (24JRRA347), National Natural Science Foundation of China (82203267), and Cuiying Scientific and Technological Innovation Program of Lanzhou Unversity Second Hospital (CY2022-MS-A12).

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Authors and Affiliations

  1. The Second Clinical Medical College, Lanzhou University, Lanzhou, China

    Yao Zhang

  2. Department of Surgical Oncology, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou, China

    Junge Deng & Jize Wang

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Correspondence to Jize Wang.

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Zhang, Y., Deng, J. & Wang, J. Cardiovascular toxicities associated with vascular endothelial growth factor receptor tyrosine kinase inhibitors: a pharmacovigilance study based on FDA adverse event reporting system. Int J Clin Pharm (2025). https://doi.org/10.1007/s11096-025-01962-8

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  • DOI  https://doi.org/10.1007/s11096-025-01962-8

Keywords

  • Cardiovascular Toxicity
  • Disproportionality Analysis
  • FAERS
  • Hypertension
  • Tyrosine Kinase Inhibitors
  • VEGFR-TKIs

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